The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro

Rárová, L.; Sedlák, David; Oklešťková, Jana; Steigerová, J.; Liebl, J.; Zahler, S.; Bartůněk, Petr; Kolář, Z.; Kohout, Ladislav; Kvasnica, Miroslav; Strnad, Miroslav

doi:https://dx.doi.org/10.1016/j.jsbmb.2018.01.005

Počet záznamů: 1

The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro

1.

SYSNO ASEP	0489630
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro
Tvůrce(i)	Rárová, L. (CZ) Sedlák, David (UMG-J)_RID Oklešťková, Jana (UEB-Q)_{RID, ORCID, SAI} Steigerová, J. (CZ) Liebl, J. (DE) Zahler, S. (DE) Bartůněk, Petr (UMG-J)_RID Kolář, Z. (CZ) Kohout, Ladislav (UEB-Q) Kvasnica, Miroslav (UEB-Q)_{RID, ORCID} Strnad, Miroslav (UEB-Q)_{RID, ORCID}
Celkový počet autorů	11
Zdroj.dok.	Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier - ISSN 0960-0760 Roč. 178, April (2018), s. 263-271
Poč.str.	9 s.
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	Brassinosteroid analog ; Cancer cell lines ; Apoptosis ; HUVEC ; Angiogenesis
Vědní obor RIV	EB - Genetika a molekulární biologie
Obor OECD	Organic chemistry
CEP	LO1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	LO1220 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	LM2015063 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	UMG-J - RVO:68378050 ; UEB-Q - RVO:61389030
UT WOS	000428483800030
DOI	10.1016/j.jsbmb.2018.01.005
Anotace	We report the synthesis and detailed biological study of the synthetic brassinosteroid analog 2 alpha,3 alpha-dihydroxy-6-oxo-5 alpha-androstan-17 beta-yl N-(tert-butoxycarbonyl)-D,L-valinate (BR4848). The panel of cancer cell lines was used for characterization of its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis was accompanied by increase of apoptotic subG(1) cells, PARP-1 and caspase-7 fragmentation, downregulation of Bcl-2 and Mcl-1, an increase in caspase activity and G(2)/M phase cell cycle arrest. Antiproliferative properties of BR4848 were exhibited by inhibition of phosphorylation of Akt, Erk1/2 and FAK. Furthermore, the developed analog exhibited in vitro antiangiogenic activity in human umbilical vein endothelial cells (HUVECs). BR4848-induced apoptosis accompanied with G2/M arrest was detected in endothelial cells. BR4848 also inhibited adhesion, tube formation and migration of endothelial cells by inhibition of FAY, Erk 1/2, CDK5, VEGFR2, TNF alpha-stimulated production of IL-6, angiopoietin-2 and Jagged1. Finally, BR4848 did not modulate the activity nor nuclear translocation of any of the steroid receptors (ER alpha, ER beta, AR, MR and PR) included in reporter cell-based assays, which excludes the genomic activity of steroid receptors as a contributing factor to the observed biological activities of BR4848.
Pracoviště	Ústav molekulární genetiky
Kontakt	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Rok sběru	2019

Počet záznamů: 1